Acta Neuropathologica

, Volume 23, Issue 3, pp 229–244 | Cite as

Pompe's disease: An inborn lysosomal disorder with storage of glycogen

A study of brain and striated muscle
  • J. J. Martin
  • Th. de Barsy
  • F. Van Hoof
  • G. Palladini
Original Investigations


Anatomopathological studies are reported in a new case of Pompe's disease (glycogenosis type II). The topography of the selective neuronal involvement is again stressed and more accurately localized regarding the thalamus. The accumulation of glycogen-filled vacuoles in astroglia, Schwann cells and myenteric plexus is demonstrated by light or electron microscopy or both.

The histochemical features of the basophilic material coexisting with glycogen in striated muscle are described. Our results indicate a close relationship between glycogen and the basophilic material; they indicate that phosphate groups may be responsible for the alcianophilia and metachromasia at low pH.

Ultrastructural studies of biopsy and autopsy specimens of striated muscle show that much of the glycogen is in vacuoles which are most probably of lysosomal nature.

Key words

Pompe's Disease Glycogen-filled Vacuoles Basophilic Substance Glycogen Lysosomes 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aparicio, S. R., Marsden, P.: Application of standard micro-anatomical staining methods to epoxy resin-embedded sections. J. clin. Path.22, 589–592 (1969).Google Scholar
  2. Barsy, Th. de, Jacquemin, P., Van Hoof, F., Hers, H. G.: Enzyme replacement in Pompe's disease. In: Enzyme replacement in genetic diseases. National Foundation Symposium Birth Defects—Original articles (in press).Google Scholar
  3. Baudhuin, P., Hers, H. G., Loeb, H.: An electron miscroscopic and biochemical study of type II glycogenosis. Lab. Invest.13, 1139–1152 (1964).Google Scholar
  4. Canal, N., Frattola, L., Pellegrini, G.: Skeletal muscle glycogenosis type II. Biochemical and electron microscopic investigations of one case. Z. Neurol.201, 98–108 (1972).Google Scholar
  5. Cardiff, R. D.: A histochemical and electron microscopic study of skeletal muscle in a case of Pompe's disease (glycogenosis II). Pediatrics37, 249–259 (1966).Google Scholar
  6. Childs, A. W., Crose, R. F., Hederson, P. H.: Glycogen disease of the heart. Report of two cases occurring in siblings. Pediatrics10, 208–217 (1952).Google Scholar
  7. Clement, D. H., Godman, G. C.: Glycogen disease resembling mongolism, cretinism and amyotonia congenita. Case report and review of the literature. J. Pediat.36, 11–30 (1950).Google Scholar
  8. Cori, G. T.: Biochemical aspects of glycogen deposition disease. Mod. Probl. Paediat.3, 344–358 (1957).Google Scholar
  9. Crome, L., Cumings, J. N., Duckett, S.: Neuropathological and neurochemical aspects of generalized glycogen storage disease. J. Neurol. Neurosurg. Psychiat.26, 422–430 (1963).Google Scholar
  10. Curran, R. C.: The histochemistry of mucopolysaccharides. Int. Rev. Cytol.17, 149–212 (1964).Google Scholar
  11. Dewulf, A.: Anatomy of the normal human thalamus. Topometry and standardized nomenclature. Amsterdam: Elsevier Publ. Comp. 1971.Google Scholar
  12. Drochmans, P.: Morphologie du glycogène. J. Ultrastruct. Res.6, 141–163 (1962).Google Scholar
  13. Dubois-Dalcq, M.: Etude histochimique des corps de Lafora. Acta neuropath. (Berl.)12, 205–217 (1969).Google Scholar
  14. Escourolle, R., Berger, B., Poirier, J.: Etude ultrastructurale d'une biopsie musculaire au cours d'une glycogénose type II. Path. europ.2, 447–457 (1967).Google Scholar
  15. French, J. E., Benditt, E. P.: The histochemistry of connective tissue: II. The effect of proteins on the selective staining of mucopolysaccharides by basic dyes. J. Histochem. Cytochem.1, 321–325 (1953).Google Scholar
  16. Gambetti, P., DiMauro, S., Baker, L.: Nervous system in Pompe's disease. Ultrastructure and biochemistry. J. Neuropath. exp. Neurol.30, 412–430 (1971).Google Scholar
  17. Ganter, P., Jollès, G.: Histochimie normale et pathologique. Paris: Gautiers-Villars 1970.Google Scholar
  18. Ganter, P., Roujeau, J., See, G.: Les glycogénoses musculaires (étude histochimique d'une forme particulière). Ann. Anat. path.10, 197–214 (1965).Google Scholar
  19. Garancis, J. C.: Type II glycogenosis. Biochemical and electron microscope study. Amer. J. Med.44, 289–300 (1968).Google Scholar
  20. Gasser, G.: Basic neuropathological technique. Oxford: Blackwell Scientific Publ. 1961.Google Scholar
  21. Gautier, M., Habib, R., Bargeton, E., Nouaille, J.: Les glycogénoses cardio-musculaires. Etude de deux cas. Sem. Hôp. Paris40, 1025–1029 (1964).Google Scholar
  22. Günther, R.: Beitrag zur Kenntnis der Glykogen-Speicherkrankheit. Virchows Arch. path. Anat.304, 87–96 (1939).Google Scholar
  23. Hers, H. G.: Recent developments in the biochemistry of glycogen storage disease and of fructose intolerance. Chem. Weekbl.57, 437–440 (1961).Google Scholar
  24. Hers, H. G.: α-Glucosidase deficiency in generalized glycogen-storage disease. (Pompe's disease). Biochem. J.86, 11–16 (1963).Google Scholar
  25. Hers, H. G.: Inborn lysosomal diseases. Gastroenterology48, 625–633 (1965).Google Scholar
  26. Hers, H. G.: The concept of inborn lysosomal disease. In: Lysosomes and storage diseases. Ed. by H. G. Hers and F. Van Hoof. New York: Academic Press 1973.Google Scholar
  27. Hers, H. G., de Barsy, Th.: Type II glycogenosis: acid maltase deficiency. In: Lysosomes and storage diseases. Ed. by H. G. Hers and F. Van Hoof. New York: Academic Press 1973.Google Scholar
  28. Hers, H. G., Van Hoof, F.: Glycogen storage diseases, type II and type VI glycogenosis. In: Carbohydrate metabolism and its disorders, Vol. II, pp. 151–160. Ed. by F. Dickens, P. J. Randle and W. Whelan. New York: Academic Press 1968.Google Scholar
  29. Heycop ten Ham, M. W. van: Lafora's disease. Review of histochemical aspects. Arch. Neurobiol. (Madr.)28, 647–666 (1965).Google Scholar
  30. Hogan, G. R., Gutmann, L., Schmidt, R., Gilbert, E.: Pompe's disease. Neurology (Minneap.)19, 894–900 (1969).Google Scholar
  31. Hug, G., Schubert, W. K.: Glycogenosis type II. Glycogen distribution in tissues. Arch. Path.84, 141–152 (1967).Google Scholar
  32. Hug, G., Garancis, J. C., Schubert, W. K., Kaplan, S.: Glycogen storage disease types II, III, VIII and IX. Amer. J. Dis. Child.111, 457–474 (1966).Google Scholar
  33. Krivit, W., Polglase, W. J., Gunn, F. D., Tyler, F. H.: Studies in disorders of muscle. IX Glycogen storage disease primarily affecting skeletal muscle and clinically resembling amyotonia congenita. Pediatrics12, 165–177 (1953).Google Scholar
  34. Lejeune, N., Thinès-Sempoux, D., Hers, H. G.: Tissue fractionation studies. Intracellular distribution and properties of alpha glucosidases in rat liver. Biochem. J.86, 16–21 (1963).Google Scholar
  35. Lison, L.: Histochimie et cytochimie animales. Paris: Gauthiers-Villars 1960.Google Scholar
  36. Loeb, H., Smulders, J., Van Thiel, E., Baran, D., Van Geffel, R.: Etude de deux cas de glycogénose généralisée avec cardiomégalie (maladie de Pompe). Rev. belge Path.30, 167–187 (1964).Google Scholar
  37. Luft, J. H.: Improvements in epoxy resin embedding methods. J. biophys. biochem. Cytol.9, 409–414 (1961).Google Scholar
  38. Mancall, E. L., Aponte, G. E., Berry, R. G.: Pompe's disease (diffuse glycogenosis) with neuronal storage. J. Neuropath. exp. Neurol.24, 85–96 (1965).Google Scholar
  39. Mekanik, G., Smith, R. L., Macleod, R. M.: Enzyme patterns in glycogen storage disease type II (Pompe's disease). Metabolism15, 641–648 (1966).Google Scholar
  40. Martin, J. J., Guazzi, G. C., de Barsy, Th.: Sur l'incidence et la signification de certaines glioses fibrillaires du tronc cérébral chez les très jeunes enfants. J. Hirnforsch.11, 7–12 (1969).Google Scholar
  41. Muller, O. F., Bellet, S., Ertrugrul, A.: Glycogen-storage disease. Report of a case with generalized glycogenosis and review of the literature. Circulation23, 261–268 (1961).Google Scholar
  42. Palladini, G., Lauro, G.: Interazione delle proteine nella colorazione agli Alcians. Ric. Sci.38, 568–573 (1968a).Google Scholar
  43. Palladini, G., Lauro, G.: Observations sur la signification de la coloration aux alcians pour les mucopolysaccharides. Histochemie16, 15–22 (1968b).Google Scholar
  44. Palladini, G., Lauro, G.: Histochimie des lipides complexes. I. Révélation des groupes vicglycols. Histochemie21, 117–122 (1970).Google Scholar
  45. Pompe, J. C.: Over idiopatische hypertrophie van het hart. Ned. T. Geneesk.76, 304–311 (1932).Google Scholar
  46. Putschar, W.: Über angeborene Glykogenspeicherkrankheit der Herzens. “Thesaurismosis glykogenica”. Beitr. path. Anat.90, 222–232 (1932).Google Scholar
  47. Ravetto, C.: Alcian blue-Alcian yellow. A new method for identification of different acidic groups. J. Histochem. Cytochem.12, 44–45 (1964).Google Scholar
  48. Reynolds, E. S.: The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J. Cell Biol.17, 208–213 (1963).Google Scholar
  49. Sakai, M., Austin, J., Witmer, F., Trueb, L.: Studies in myoclonus epilepsy (Lafora body form). II. Polyglucosans in teh systemic deposits of myoclonus epilepsy and in corpora amylacea. Neurology (Minneap.)20, 160–176 (1970).Google Scholar
  50. Sandritter, W., Kiefer, G., Rick, P.: Über die Stöchiometrie von Gallocyaninchromoalun mit Desoxyribonukleinsäure. Histochemie3, 315–340 (1963).Google Scholar
  51. Sandström, N., Westman, J., Öckerman, P. A.: Glycogenosis of the central nervous system in the cat. Acta neuropath. (Berl.)14, 194–200 (1969).Google Scholar
  52. Schanabel, R.: Über die neuromuskuläre Form der Glykogenspeicherungskrankheit. Virchows Arch. path. Anat.331, 287–313 (1958a).Google Scholar
  53. Schnabel, R.: Histochemische Untersuchungen über die “basophile Substanz” der Skeletmuskulatur bei Glykogenose. Virchows Arch. path. Anat.331, 536–544 (1958b).Google Scholar
  54. Schnabel, R.: Über die Speicherung mucopolysaccharidartigen Substanzen im Gehirn bei generalisierter Glykogenose (Typ II). Acta neuropath. (Berl.)4, 646–658 (1965).Google Scholar
  55. Schnabel, R.: Zur Histochemie der mucopolysaccharidartigen Substanzen (basophile Substanzen) in der Skeletmuskulatur bei neuromuskulärer Glykogenose (Typ II). Acta neuropath. (Berl.)17, 169–178 (1971).Google Scholar
  56. Schnabel, R., Seitelberger, F.: Histochemische Studien an Myoklonuskörpern bei progressiver Myoklonusepilepsie (Typ Unverricht). Acta neuropath. (Berl.)14, 19–37 (1969).Google Scholar
  57. Sidbury, J. B.: The genetics of the glycogen storage disease. In: Progress in Medical Genetics, Vol. 4, Chapt. 2, pp. 32–58. Eds. A. G. Steinberg and A. G. Bearn. New York: Grune and Stratton Inc. 1965.Google Scholar
  58. Sjöstrand, F. S.: Electron microscopy of cells and tissues, Vol. I. Instrumentation and techniques. New York: Academic Press 1967.Google Scholar
  59. Smith, J., Zellweger, H., Afifi, K.: Muscular form of glycogenosis type II (Pompe). Report of a case with unusual features. Neurology (Minneap.)17, 537–549 (1967).Google Scholar
  60. Thiéry, J. P.: Mise en évidence des polysaccharides sur coupes fines en microscopie électronique. J. Microscopie6, 987–1018 (1967).Google Scholar
  61. Toussaint, D., Danis, P.: Ocular histopathology in generalized glycogenosis (Pompe's disease). Arch. Ophthal.73, 342–349 (1965).Google Scholar
  62. Van Hoof, F., Hue, L., de Barsy, Th., Jacquemin, P., Devos, P., Hers, H. G.: Gycogen storage diseases. Biochimie54, 745–751 (1972).Google Scholar
  63. Watson, M. L.: Staining of tissue sections for electron microscopy with heavy metals. J. biophys. biochem. Cytol.4, 475–478, 727–730 (1958).Google Scholar
  64. Wolfe, H. J., Cohen, R. B.: Non glycogen polysaccharide storage in glycogenosis type II (Pompe's disease). Arch. Path.86, 579–584 (1968).Google Scholar
  65. Zellweger, H., Dark, A., Abu Haidar, G. A.: Glycogen disease of skeletal muscle. Report of two cases and review of literature. Pediatrics15, 715–732 (1955).Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • J. J. Martin
    • 1
    • 2
  • Th. de Barsy
    • 1
    • 2
  • F. Van Hoof
    • 1
    • 2
  • G. Palladini
    • 1
    • 2
    • 3
  1. 1.Department of NeuropathologyBorn-Bunge FoundationBerchem(Antwerp)Belgium
  2. 2.Laboratoire de Chimie PhysiologiqueUniversité de LouvainLeuvenBelgium
  3. 3.Istituto di Anatomia comparata „B. Grassi”RomaItaly

Personalised recommendations